Please use this identifier to cite or link to this item:
https://hdl.handle.net/1959.11/57164
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Legendre, Sarah Veronique Anne-Marrie | en |
dc.contributor.author | Greatrex, Ben | en |
dc.contributor.author | Wilkinson, Brendan | en |
dc.date.accessioned | 2024-01-05T02:42:24Z | - |
dc.date.available | 2024-01-05T02:42:24Z | - |
dc.date.created | 2020-01 | - |
dc.date.issued | 2020-05-06 | - |
dc.identifier.uri | https://hdl.handle.net/1959.11/57164 | - |
dc.description | <p>Please contact rune@une.edu.au if you require access to this thesis for the purpose of research or study.</p> <p>Chancellor's Doctoral Research Medal was presented to the student on 6/5/20.</p> | en |
dc.description.abstract | <p>Five industry-relevant animal experiments were completed to investigate amino acid supplementation in reduced protein diets and the impacts on meat-chicken performance, metabolism, and physiology. Specifically, the role of the non-<p>The incorporation of oxygen and nitrogen atoms into a molecular skeleton is highly important in organic synthesis as many bioactive compounds contain heteroatoms within their structure. Endoperoxides are versatile molecules that are present among natural and bioactive compounds and can be used to introduce oxygen atoms during syntheses. The aim of this thesis was to investigate the reactivity of 3,6-dihydro-1,2-dioxines under basic conditions to generate enantioenriched and potentially bioactive compounds.</p> <p>In Chapter 2, a library of 1,2-dioxines was generated from the addition of singlet oxygen to 1,3-butadienes via a photooxygenation process. The <i>meso</i>-endoperoxides <b>I</b> reacted with catalyst <b>II</b> via an organocatalytic enantioselective Kornblum-DeLaMare rearrangement affording hydroxyketone products<b>III</b> with er up to 98:2. The newly formed hydroxyketones <b>III</b> were employed in the synthesis of enantioenriched lactones <b>IV</b> (er up to 89:11). Unsymmetrical endoperoxides <b>V</b> were subjected to a kinetic resolution generating highly enantioenriched 1,2-dioxines <b>VII</b> (er up to 99:1).</p> <p>In Chapter 3, endoperoxides <b>VIII</b> were reacted with primary and secondary amines via a domino Kornblum-DeLaMare/aza-Michael reaction generating a library of 12 novel aminoketones <b>IX</b> in excellent yields (71–100%) that were selectively reduced using a combination of SnCl<sub>4</sub>/NaBH<sub>4</sub> (dr up to 93:7). The stereochemistry of the diol series <b>X</b> was determined via a crystal structure and a conserved coupling pattern observed through all 1H NMR spectra. This novel reaction permitted the insertion of nitrogen atoms into structures already containing oxygen atoms and was then applied in targeted synthesis (Chapter 4).</p> <p>The novel domino reaction was successfully employed in Chapter 4 for the synthesis of (±)-HPA-12 (<b>XI</b>), an inhibitor of the CERT protein, in 4 steps from 1,2-dioxine <b>VIII</b> (34% overall yield). A library of 8 HPA-12 bioisosteres was generated by the addition of Nheterocyclic amines, the library was then biologically tested resulting in the discovery of hydrazide <b>XII</b>, found to be active against Gram-positive bacteria <i>Bacillus subtilis</i> (15.6 µg/mol) and <i>Staphylococcus aureus</i> (12–16 µg/mol).</p> | en |
dc.language | en | en |
dc.publisher | University of New England | - |
dc.title | Organocatalytic Kornblum-DeLaMare Reactions of Endoperoxides and Applications in Drug Discovery | en |
dc.type | Thesis Doctoral | en |
local.contributor.firstname | Sarah Veronique Anne-Marrie | en |
local.contributor.firstname | Ben | en |
local.contributor.firstname | Brendan | en |
local.hos.email | st-sabl@une.edu.au | en |
local.thesis.passed | Passed | en |
local.thesis.degreelevel | Doctoral | en |
local.thesis.degreename | Doctor of Philosophy - PhD | en |
local.contributor.grantor | University of New England | - |
local.profile.school | School of Science and Technology | en |
local.profile.school | School of Rural Medicine | en |
local.profile.school | School of Science and Technology | en |
local.profile.email | slegend2@une.edu.au | en |
local.profile.email | bgreatre@une.edu.au | en |
local.profile.email | bwilkin7@une.edu.au | en |
local.output.category | T2 | en |
local.record.place | au | en |
local.record.institution | University of New England | en |
local.publisher.place | Armidale, Australia | - |
local.contributor.lastname | Legendre | en |
local.contributor.lastname | Greatrex | en |
local.contributor.lastname | Wilkinson | en |
dc.identifier.staff | une-id:slegend2 | en |
dc.identifier.staff | une-id:bgreatre | en |
dc.identifier.staff | une-id:bwilkin7 | en |
local.profile.orcid | 0000-0002-0356-4966 | en |
local.profile.orcid | 0000-0003-1866-6540 | en |
local.profile.role | author | en |
local.profile.role | supervisor | en |
local.profile.role | supervisor | en |
local.identifier.unepublicationid | une:1959.11/57164 | en |
dc.identifier.academiclevel | Student | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
local.thesis.bypublication | No | en |
local.title.maintitle | Organocatalytic Kornblum-DeLaMare Reactions of Endoperoxides and Applications in Drug Discovery | en |
local.relation.fundingsourcenote | IPRA scholarship. | en |
local.output.categorydescription | T2 Thesis - Doctorate by Research | en |
local.relation.doi | 10.1016/j.tet.2017.11.010 | en |
local.school.graduation | School of Science & Technology | en |
local.thesis.borndigital | Yes | - |
local.search.author | Legendre, Sarah Veronique Anne-Marrie | en |
local.search.supervisor | Greatrex, Ben | en |
local.search.supervisor | Wilkinson, Brendan | en |
local.uneassociation | Yes | en |
local.atsiresearch | No | en |
local.sensitive.cultural | No | en |
local.year.conferred | 2020 | en |
local.subject.for2020 | 340401 Biologically active molecules | en |
local.subject.for2020 | 340503 Organic chemical synthesis | en |
local.subject.seo2020 | 240908 Organic industrial chemicals (excl. resins, rubber and plastics) | en |
local.subject.seo2020 | 280105 Expanding knowledge in the chemical sciences | en |
local.profile.affiliationtype | UNE Affiliation | en |
local.profile.affiliationtype | UNE Affiliation | en |
local.profile.affiliationtype | UNE Affiliation | en |
Appears in Collections: | School of Rural Medicine School of Science and Technology Thesis Doctoral |
Files in This Item:
File | Description | Size | Format |
---|
Page view(s)
508
checked on Jun 30, 2024
Download(s)
6
checked on Jun 30, 2024
Items in Research UNE are protected by copyright, with all rights reserved, unless otherwise indicated.